Oregon is one of a few states where methamphetamine (MA) abusers without a greater history of cocaine abuse are recruited for clinical research. The Methamphetamine Abuse Research Center (MARC) will characterize effects of MA administration and withdrawal at molecular, neurochemical, anatomical, behavioral, and clinical levels, to identify obstacles to recovery in MA abusers. Overarching themes addressed in preclinical and clinical research components using common methodologies include neuroadaptation to MA, neuroanatomy of MA-related behaviors, stressor responsivity, and impulsivity. Human and animal protocols inform one another with respect to these themes, forming the basis for bidirectional translational research. The Center's Administrative Core facilitates interactions among MARC investigators, and the Biostatistics Core analyzes associations and correlations within and across components. The Animal Core breeds and maintains genetically selected lines and other strains, and provides them to MARC investigators. The Education Core coordinates the research training of M.D. and Ph.D. pre- and postdoctoral fellows, and organizes and disseminates both clinical and preclinical information from MARC investigators to Centers and Oregon's rural areas that are impacted by MA production and abuse. Scientific Component 5 correlates acetylcholine release with active and passive administration of MA and provides neuroanatomic and molecular signaling data relevant to MA seeking for use in other components. Scientific Component 6, examines genetic influences, and behavioral and neurochemical correlates (in collaboration with Component 5) in mice selected for differences in MA-induced neuroadaptation and MA self-administration. Nomination of genetic candidates from this preclinical work could inform treatment strategies in clinical Component 7, and specific genetic associations can be pursued in patients from clinical components. Scientific Component 7 evaluates the relationship between symptom severity at intake and treatment failure in inpatients, tests (3-receptor and cholinergic medications, and conducts human laboratory evaluations of stressor responsivity. Component 8, the Pilot Projects, provides a means to support the development of multiple new directions in research on MA abuse. Thus, the MARC's themes address clinically relevant issues using innovative multidisciplinary approaches.